Practical application of the neuroregenerative properties of ketamine: real world treatment experience.

Abstract

While controversial, ketamine has emerged as an effective treatment for refractory depression. Serial infusions have been performed 3 times per week, but our practical experience has challenged this precept concerning infusion frequency. Depression is associated with neuron loss, reduced synapse numbers, and dearborization of dendrites. Ketamine appears to potently induce mechanisms which reverse these neurodegenerative processes. Ketamine not only blocks the glutamate receptor, it activates eukaroyotic elongation factor 2 (eEF2). This, in turn, activates brain-derived neurotrophic factor (BDNF) protein synthesis. This is thought to underlie ketamine's enduring benefits. In addition, ketamine alters glycogen synthase kinase-3 (GSK-3) phosphorylation, probably responsible for its rapid antidepressant effect. Notably, inhibition of the BDNF receptor does not block the immediate benefits of ketamine, but does prevent the enduring effects. Neuro-Luminance Ketamine Infusion Centers have been treating patients with serial ketamine infusions for over three years. Our methods differ from what is often reported, as we perform infusions only once per week and generally do not perform more than five infusions. Data from 100 patients showed that 80% of the patients responded. The baseline Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) score was 17.8 ± 2.8. Responders to ketamine showed a drop in QIDS-SR score of 10.8 ± 3.5, while non-responders showed a 0.8 ± 1.8 change. Moreover, they often had persistent benefits over several months. Recently, it was proposed that psychotomimetic effects are necessary during a ketamine infusion to yield effective antidepressant benefits. Yet, only one patient in our clinic has experienced hallucinations in three years. Nevertheless, 80% of our patients show clinical improvement. Further studies of clinical methods for ketamine infusion therapy are encouraged.

Changes in depression scale score.Change in Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) score was 10.8 ± 3.5 among the 80% of patients who responded to ketamine infusions, while non-responders showed a 0.8 ± 1.8 change. Weekly or even less frequent ketamine infusions appeared to yield effective long-term antidepressant benefits. Activation of brain-derived neurotrophic factor (BDNF) appears to have an important role in the antidepressant effects of ketamine. BDNF induces synaptogenesis, dendritic arborization, improved neuronal health, and neurogenesis. These processes likely underlie the persistent benefits of ketamine.